Triethylamine → (R)-1-(2-Amino-5-bromo-pyridin-3-ylmethyl)pyrrolidine-2-carboxylic acid methyl ester

HRID 1362060Notes

Reaction equation

HRID 1362060 reaction equation
Br.[Br:2][C:3]1[CH:4]=[C:5]([CH2:10]Br)[C:6]([NH2:9])=[N:7][CH:8]=1.Cl.[CH3:13][O:14][C:15](=[O:21])[C@H:16]1[CH2:20][CH2:19][CH2:18][NH:17]1.C(N(CC)CC)C>CC#N.O>[CH3:13][O:14][C:15]([C@H:16]1[CH2:20][CH2:19][CH2:18][N:17]1[CH2:10][C:5]1[C:6]([NH2:9])=[N:7][CH:8]=[C:3]([Br:2])[CH:4]=1)=[O:21]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 44629857Methyl D-prolinate hydrochlorideHCID 534200525-Bromo-3-(bromomethyl)pyridin-2-amine hydrobromide

Product 1

HCID 59456924(R)-1-(2-Amino-5-bromo-pyridin-3-ylmethyl)pyrrolidine-2-carboxylic acid methyl esterYield 90.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent2×

Procedure

A suspension of 5-bromo-3-bromomethyl-pyridin-2-ylamine hydrobromide (8.00 g, 23.1 mmol) and D-proline methyl ester hydrochloride (4.53 g, 27.4 mmol) in CH3CN (100 mL) was treated with a solution of triethylamine (10.4 mL, 74.0 mmol) in CH3CN (100 mL). After stirring at room temperature for 5 h, the cloudy mixture was diluted with H2O (300 mL) and extracted with EtOAc (3×200 mL). The combined organic layers were washed with brine (100 mL), dried over Na2SO4, filtered and the solvent was removed in vacuo. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH, 99:1 to 98:2) gave the title compound (6.55 g, 90%) as a colorless oil: MS (ESI) m/e 314 (M+H)+

Workup

  1. extractionextracted with EtOAc (3×200 mL)
  2. washThe combined organic layers were washed with brine (100 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customthe solvent was removed in vacuo
  6. customPurification by flash column chromatography (silica gel, CH2Cl2/MeOH, 99:1 to 98:2)

Sources & evidence

ORD record
ord-7a63368de50e4768acee0fd77132dafe
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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